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Biomedical subjects

H D Heck

Publications and source records attributed to H D Heck.

36 records · Page 2Linked to original sources
PubMed1983

Localization of 1,6-[14C]diaminohexane (HMDA) in the prostate and the effects of HMDA on early gestation in Fischer-344 rats.

Following oral administration of 1,6-[14C]diaminohexane (hexamethylenediamine, HMDA) to male Fischer-344 rats, approx. 20% of the administered dose was recovered as 14CO2 after 72 h. Urinary and fecal excretion accounted for 47% and 27% of the administered radioactivity, respectively. Of several tissues examined, the highest concentrations of residual radioactivity were found in the prostate at 24 and 72 h post-administration. Daily administration of HMDA (200 mg/kg/day) by gavage to pregnant female rats for 2 weeks starting on gestation day 0 did not affect litter size in these animals.

Animals↗
PubMed1983

Sulfhydryl oxidation in rat nasal mucosal tissues after chlorine inhalation.

Male F-344 rats were exposed to target concentrations of 2.5, 5, or 10 ppm Cl2 for various amounts of time, after which respiratory and olfactory nasal mucosal tissues were analyzed for changes in total sulfhydryl (TSH) content. No changes in olfactory mucosa TSH content were observed at the maximum Cl2 exposure. Decreases in content of respiratory mucosa TSH were seen after 6 hr exposures to 5 ppm and 10 ppm, but not 2.5 ppm. The concentration of TSH returned to control values 19 hr after termination of exposure. Analysis of TSH changes in concentration X time (CT) studies suggested that decreases in TSH were dependent on the airborne concentration of Cl2 and not on 'dose' (the CT product). The results suggest that inhaled Cl2 can oxidize tissue sulfhydryl groups at the point of entry, but not at deeper regions of the respiratory tract.

Administration, Intranasal↗
PubMed1982

Determination of formaldehyde in biological tissues by gas chromatography/mass spectrometry.

A quantitative method is described for the determination of formaldehyde in biological tissues by stable isotope dilution using gas chromatography/mass spectrometry. (13C2H2)Formaldehyde is used as the isotopic diluent. After tissue homogenization, derivatization is carried out in situ with pentafluorophenylhydrazine, followed by extraction and analysis using selected ion monitoring. The sensitivity of the technique is higher than that of conventional methods of formaldehyde analysis, enabling endogenous formaldehyde to be quantitatively analyzed in tissues, even in samples as small as 20 mg wet weight. The effects of exposure to airborne formaldehyde or to airborne methyl chloride on the formaldehyde concentrations of several tissues of Fischer-344 rats are reported.

Animals↗
PubMed1979

Simultaneous determination of n-hexane, 2-hexanone and 2,5-hexanedione in biological tissues by gas chromatography mass spectrometry.

A quantitative method is reported for the determination of n-hexane, 2-hexanone and 2,5-hexanedione in biological tissues by stable isotope dilution using gas chromatography mass spectrometry. n-[2H14]Hexane, 2-[2H5]hexanone and 2,5-[2H10]hexanedione are used as the isotopic diluents. After tissue homogenization and extraction of the three compounds in the presence of the deuterated internal standards, analysis is carried out in a single gas chromatographic injection by selected ion monitoring. Principal advantages of the technique are the ease of sample handling, rapidity of analysis and low limits of detection. The methodology is used to determine the organ distribution, pharmacokinetics and metabolism of n-hexane to 2-hexanone and 2,5-hexanedione in rats following inhalation exposure.

Animals↗
PubMed1978

The measurement of cell turnover rates using stable isotope-labelled thymidine: experiments on the small intestine and on a transplantable lymphatic tumour of the mouse.

Multilabelled, non-radioactive thymidine and tritiated thymidine were incorporated simultaneously into the DNA of a rapidly-growing, transplantable mouse lymphoma and the DNA of mouse small intestine by a single intraperitoneal injection of both labelled nucleosides. Mice were killed at selected times during the next 7 days, and the specific activities of the tissues and extracted DNA and the 132/126 mass ratio of thymine isolated from the DNA were determined by scintillation counting and by field ionization mass spectrometry respectively. The rates of decrease of the concentrations of tritiated and stable isotope-labelled thymine in the DNA of the tumour or of the intestine were essentially identical. These results indicate the feasibility of using thymidine multilabelled with stable isotopes for measurement of cell turnover rates in conjunction with cancer therapy.

Animals↗
PubMed1977

A stable isotope method for measurement of thymidine incorporation into DNA.

A method has been developed for the measurement of DNA synthesis in vivo using the incorporation of multilabeled, non-radioactive thymidine. Simultaneous intraperitoneal injection of hexalabeled thymidine and tritiated thymidine into a normal adult rat resulted in the incorporation of both labeled nucelosides into the DNA of cells undergoing replication. The DNA of several tissues and organs was analysed, including liver, thymus, spleen, bone marrow, and small intestine. Following extraction with hot trichloroacetic acid, acid hydrolysis, and thin-layer chromatography of the hydrolysates, the isotopic compositions of the thymine products were determined by field ionization mass spectrometry and by scintillation counting. The relative incorporation of radioactive and stable isotope-labeled thymidine was similar in all tissues, and corresponded to the ratio of the two labeled nucleosides in the injected material. These results indicate the feasibility of utilizing thymidine multilabeled with stable isotopes for measurement of cellular proliferation rates in conjunction with cancer therapy.

Animals↗
PubMed1968

The resolution of some steps of the reactions of lactate dehydrogenase with its substrates.

1. The reaction of pig heart lactate dehydrogenase (EC 1.1.1.27) with NAD(+) and lactate to form pyruvate and NADH was followed by rapid spectrophotometric methods. The distinct spectrum of enzyme-bound NADH permits the measurement of the rate of dissociation of this compound. 2. The reduction of the first mole equivalent of NAD(+) per mole of enzyme sites can also be observed, and is much more rapid than the steady-state rate of NADH production. 3. At pH8 the dissociation of the enzyme-NADH complex is rate-determining for the steady-state oxidation of lactate. At lower pH some other step after the interconversion of the ternary complex and before the dissociation of NADH is rate-determining. Other evidence for a compulsory-order mechanism is provided.

Animals↗
PubMedDate not supplied

Chemical urolithiasis 2. Thermodynamic aspects of bladder stone induction by terephthalic acid and dimethyl terephthalate in weanling Fischer-344 rats.

The induction of calcium terephthalate (CaTPA) calculi in the urinary tract of rats ingesting terephthalic acid (TPA) or dimethyl terephthalate is a result of supersaturation with respect to the stone components. The solubility product of CaTPA was determined in water at 37 degrees C, and its value in urine of exposed weanling Fischer-344 rats was calculated based on the electrolyte concentrations of freshly-collected, microliter urine samples. The value of the solubility product in urine is equal to the minimum concentration product of free Ca2+ and TPA2- at which crystallization can occur; hence, the urinary solubility product is a parameter that is useful for risk assessment. Estimates of the TPA concentrations required to induce crystals or stones in normal human urine are presented.

Animals↗
PubMedDate not supplied

Disposition and pharmacokinetics of inhaled dimethylamine in the Fischer 344 rat.

The disposition and pharmacokinetics of [14C]dimethylamine [( 14C] DMA) following 6-hr inhalation of either 10 or 175 ppm were determined in male Fischer 344 rats. Seventy-two hours after termination of exposure, the disposition of recovered radioactivity was similar for each airborne concentration, with more than 90% in the urine and feces, 7 to 8% in selected tissues and the carcass, and 1.5% exhaled as 14CO2. Over 98% of the radioactivity in the urine was unmetabolized DMA. Analysis of tissue radioactivity immediately after exposure to [14C]DMA showed that the respiratory nasal mucosa contained the highest concentration of 14C, followed by the olfactory nasal mucosa; concentrations of 14C in liver, lung, kidney, brain, and testes were approximately 2 orders of magnitude less than in the nasal mucosal tissues. Radioactivity in plasma of rats exposed by inhalation to 175 ppm of [14C]DMA decayed in a biphasic manner. The terminal half-life for plasma radioactivity was similar to the half-lives of some plasma proteins, suggesting incorporation of 14C into proteins subsequent to metabolism of [14C]DMA. The results indicate that, while most of the inhaled DMA is excreted unchanged, a small amount of oxidative metabolism of DMA occurs.

Animals↗
PubMedDate not supplied

Metabolism of dimethylamine in the nasal mucosa of the Fischer 344 rat.

The metabolism of dimethylamine (DMA) in the nasal mucosa of the male Fischer 344 rat was investigated in vitro and in vivo. Microsomes were prepared from liver, and from respiratory and olfactory nasal mucosa. All microsomal preparations metabolized DMA to formaldehyde (CH2O), though DMA was a poor substrate for the N-demethylation reaction when compared to benzphetamine. Phenobarbital-induced microsomes metabolized DMA at a rate less than that of control. The results indicated that DMA was a substrate for both cytochrome P-450 and FAD-containing monooxygenase, and that both enzyme activities were present in all microsomal preparations. Finally, unextractable radioactivity was observed in DNA, RNA, and protein isolated from respiratory and olfactory mucosa of rats exposed to either 10 or 175 ppm of [14C]DMA, suggesting metabolism of [14C]DMA to 14CH20 with subsequent incorporation of 14C into macromolecules. The results demonstrate that the respiratory and olfactory nasal mucosa have the capability to metabolize DMA to CH2O, and indicate that such metabolism occurs in vivo.

Aniline Compounds↗